The long-term goal of this study is the elucidation of some ultrastructural and neurochemical correlates of mental deficiency. The approach being used is experimental intervention in th maturation of the mammalian brain with subsequent measurement of selected parameters, changes in which are likely to underlie mental retardation. The following animal models of mental deficiency are being used:(1) Perinatally malnourished rats (8% protein diet throughout gestation, lactation and until studies are performed); (2) Neonatally cretinized rats (injected intraperitoneally with 131iodine 150-200 Ci on the day of birth). The following morphological and cytochemical synaptic characteristics will be assessed at 35 and at 90-120 days postnatally in experimental and control animals: (a) types of synapses based on cleft width and vesicle form, the appearance of mitochondria near synapses, and the presence of any structural anomalies in pre- or postsynaptic elements as demonstrated in aldehyde-osmium tetroxide fixed tissue from specific brain regions; (b) configurational changes in synaptic profiles as revealed by ethanolic-phosphotungstic acid (E-PTA) block-staining of previously gluteraldehyde-fixed tissue from the same brain regions; and (c) the degree of disruption and structural characteristics of synaptic junctional complexes (SJC) in purified synaptosomal preparations of cerebral cortex, and whole brain using both aldehyde-osmium tetroxidefixation and E-PTA pellet-staining after glutaraldehyde fixation. Norepinephrine, dopamine and serotonin content and turnover rates of the cerebral cortex and whole brain will be determined. Comparison of findings in two selected animal models of mental deficiency with controls should help to elucidate the ultrastructural and neurohistochemical bases of mental retardation.